Note on the formulation of thermosensitive and mucoadhesive vaginal hydrogels containing the miniCD4 M48U1 as anti-HIV-1 microbicide

The miniCD4 M48U1 was formulated into thermosensitive and mucoadhesive pluronic^® hydrogels as anti-HIV-1 microbicide. The release kinetics of M48U1 from F127/HPMC (20/1 wt%) and F127/F68/HPMC (22.5/2.5/1 wt%) studied during 24 h by using Franz diffusion cells showed that HEC hydrogel (1.5 wt%) used as control released 93% of the peptide, while about 25% of M48U1 remained in pluronic^® hydrogels. The formulation of M48U1 in pluronic^® hydrogels ensures a local delivery because no diffusion of the peptide was detected through vaginal Cynomolgus macaque mucosa using Ussing chamber. Finally, toxicological studies showed no significant difference in the HeLa cell viability of the pluronic^® hydrogels in comparison with HEC and phosphate buffer saline.     

Formulation of thermoresponsive and bioadhesive gel for treatment of oesophageal pain and inflammation

The aim of this study was the formulation and examination of a novel thermoresponsive and bioadhesive, in situ gelling drug delivery system, which can be used in the treatment of oesophageal pain and inflammation. A bioadhesive cellulose derivative (Metolose^® 60SH) was used as a thermoresponsive material, because Metolose^® has thermal gelation properties at certain temperature. The thermal gelation temperature (T₂) of Metolose^® 60SH 2 w/w% solution is above body temperature (65-66 °C), but by using different methods (Metolose^® 60SH concentration, auxiliary materials), it can be shifted near to body temperature. The pH alteration between pH = 2-10 and the application of different alcohols did not influence the gelation temperature, but using water-soluble salts and changing the concentration of Metolose^® 60SH solution between 2 and 3 w/w% the thermal gelation point could be decreased. Different NSAIDs were used as model drugs and which had not influence on thermal gelation temperature, but difference in in vitro liberation and penetration can be observed. In vitro adhesion test pointed out that the condition of investigated membrane can change the adhesion. Morphological test of oesophageal tissue showed that investigated materials had no irritative or tissue-damaging effect on the oesophageal mucosa even after 12 h.     

Understanding the structure and stability of paclitaxel nanocrystals

Previously, PTX/Pluronic F127 nanocrystals were prepared in our laboratory using the stabilization of nanocrystals (SNC) method. For PTX nanocrystals, dosages could be increased to yield improved antitumor activity over Taxol^® without incidence of acute toxicity. The objectives of this current study are to further understand the structure and stability of PTX nanocrystals. More Pluronic F127 surfactant was added in the formulation to attempt to further stabilize the nanocrystals against thermal induced aggregation. However, this resulted in formation of micelles that worsened the stability of nanocrystals. The F127 desorption experiment suggested different surfactant adsorption affinity to nanocrystal surface below and above the CMC. Below the CMC monomers bound to nanocrystal surface with high affinity, but above the CMC low affinity surfactant aggregates readily left the surface upon dilution. At higher temperature the tendency of F127 micellization is enhanced due to drastically lower CMC. Consequently, at 37 °C there was F127 desorption even for nanocrystals prepared with low amounts of F127 (1:5 (w/w) PTX/F127). To improve the stability of nanocrystals, re-nanonization by incubation–sonication procedure was used to disrupt the preferred crystal growth pattern of PTX. Furthermore, we have demonstrated that a higher heating temperature (45 °C vs. 37 °C) used in the incubation–sonication procedure was able to provide even better nanocrystal stability for long periods of incubation time.     

Development and characterization of micellar systems for application as insect repellents

N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent due to its high efficacy. In this work, micellar systems based on poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) triblock copolymer were developed and studied for the purpose of controlling the release and cutaneous permeation of DEET, using concentrated solutions of the copolymer Pluronic F127 to form thermoreversible gels. The formulations presented thermoreversible gelation above 5 °C and altered rheological behavior at 15 and 25 °C. The presence of the drug drastically changed the sol–gel transition temperatures. The micrographs suggest that DEET induced the formation of anisotropic structures, and Maltese Crosses were observed. The formulation containing 10 wt% DEET and 15 wt% Pluronic F127 presented sustained drug release for up to 7 h. DEET release profile followed the Higuchi kinetics model. There was a reduction of approximately 35% in the amount of DEET absorbed through the skin after 6 h. About 62% of DEET from the formulation consisting of Pluronic F127 and DEET remain retained on the skin. The anisotropic structure may constitute a barrier to diffusion and thereby controlling the drug release effectively. These tests suggest that the tested samples exhibit safety profile greater than some commercially available products.     

Characterization and Antimicrobial Activity of N-Methyl-2-pyrrolidone-loaded Ethylene Oxide-Propylene Oxide Block Copolymer Thermosensitive Gel

The purpose of this study is to investigate the effects of N-methyl-2-pyrrolidone on the thermosensitive properties of aqueous ethylene oxide-propylene oxide block copolymer (Lutrol^® F127) system. Due to the aqueous solubility enhancement and biocompatibility, N-methyl-2-pyrrolidone is an interesting solubilizer for the poorly water soluble drugs to be incorporated in the Lutrol^® F127 system. Effect of N-methyl-2-pyrrolidone on physicochemical properties of Lutrol^® F127 system was investigated using appearance, pH, gelation, gel melting temperature and rheology. The antimicrobial activity of the thermosensitive N-methyl-2-pyrrolidone gel was also tested. Lower N-methyl-2-pyrrolidone amount (≤30%w/w) could shift the sol-gel transition to a lower temperature but the gel-sol transition was shifted to a higher temperature. Higher N-methyl-2-pyrrolidone (≥40%w/w) could shift both sol-gel and gel-sol transitions of the system to a lower temperature. The amount of N-methyl-2-pyrrolidone >60% w/w could reverse the phase of the Lutrol^® F127 system to non-newtonian flow at 4° and Newtonian flow at high temperature. Aqueous Lutrol^® F127 system containing N-methyl-2-pyrrolidone exhibited antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans with the N-methyl-2-pyrrolidone in a dose-dependent manner.     

Ultrasonic velocity and light-scattering studies on the polyoxyethylene—polyoxypropylene copolymer Pluronic F127 in aqueous solution

Ultrasonic velocity and light-scattering measurements on aqueous solutions of the ABA polyoxyethylene-polyoxypropylene block copolymer, Pluronic F127, have clearly indicated a micellar mode of association over the temperature range 10–40°C. The extent of association was limited below 25°C but increased markedly at higher temperatures giving micelles with a mean weight-average aggregation number of 44 at 40°C. A pronounced decrease in the critical micelle concentration accompanied the micellar enlargement. Aggregates were asymmetric at low temperatures but increased in symmetry with temperature increase becoming spheroidal above 25°C.A theoretical treatment of the concentration-dependent changes in ultrasonic velocity is proposed from which information concerning the volume change on micellization may be obtained. Micellization of F127 over the temperature range 20–30°C has been shown to be associated with a very small change in the molar volume of the monomers and this volume change decreased with increases in temperature to the extent of 2%/°C. The temperature-dependent changes in micellar properties have been related to the reversible thermal gelation of this block copolymer.     

Thermosetting microemulsions and mixed micellar solutions as drug delivery systems for periodontal anesthesia

In the present study, thermosetting microemulsions and mixed micellar solutions were investigated as drug delivery systems for anesthetizing the periodontal pocket. The structure of the systems, consisting of the active ingredients lidocaine and prilocaine, as well as two block copolymers (Lutrol F127 and Lutrol F68), was investigated by NMR spectroscopy and photon correlation spectroscopy (PCS). The results obtained for dilute (1-3% w/w) solutions show discrete micelles with a diameter of 20-30 nm and a critical micellization temperature of 25-35 degrees C. Gel permeation chromatography (GPC) was used to study the distribution of the active ingredients, and indicates a preferential solubilization of the active components in micelles over unimers. Analogous to the Lutrol F127 single component system these formulations display an abrupt gelation on increasing temperature. The gelation temperature was found to depend on both the drug ionization and concentration. These systems have several advantages over emulsion-based formulations including good stability, ease of preparation, increased drug release rate, and improved handling due to the transparency of the formulations.     

Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) – Pluronic® F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez^® AN, GZ) and Pluronic^® F127 (PF127) copolymers (GZ–PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol–gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.     

Solubilization of the chlorin TPCS2a in the presence of Pluronic® F127/Tween 80 mixtures

The efficacy of surfactant mixtures of Pluronic^® F127 and Tween 80 at overall concentration in the micromolar range and molar ratio 1:1, 1:10, and 10:1 in inhibiting aggregation of the photosensitizer meso-tetraphenyl chlorin disulphonate (TPCS_2a) was investigated in aqueous media at pH 2.9 by means of steady-state absorption and fluorescence emission spectroscopy as well as time-resolved fluorescence analysis. Corresponding experiments were performed at pH 7.4 in the absence of surfactants to determine the spectroscopic properties of a monomeric sample. Aggregation resulted in a red shift of the Soret absorption band and in substantial fluorescence quenching. The fluorescence lifetime of TPCS_2a was a particularly sensitive indicator of the aggregation state, as the monomer at pH 7.4 decayed with a?～?10?ns time constant, while aggregation resulted in subnanosecond decay. The critical micelle concentration (CMC) of the surfactant mixtures was determined spectrophotometrically in the presence of TPCS_2a. The ability of the surfactant mixtures to prevent aggregation at acidic pH was evaluated at overall surfactant concentration below and above CMC. Solubilization of TPCS_2a in Pluronic^® F127/Tween 80 mixtures prevented aggregation of the photosensitizer at overall surfactant concentrations much lower than those needed for both pure Pluronic^® F127 and pure Tween 80.     

Plasticizer extraction of Taxol?-infusion solution from various infusion devices

Taxol^® solution extracts the plasticizer DEHP (di(2-ethylhexyl)phthalate) from polyvinyl chloride (PVC) materials. In order to minimize patient exposure to DEHP, Taxol^® solutions should be prepared and administered in PVC-free materials. Particulate matter may form in Taxol^® infusion solution over time, so that in-line filtration with microporous membranes not greater than 0.22 m is advisable. The purpose of this study was to evaluate the suitability of various administration- and in-line filter-sets for Taxol^® application. The extent of leached DEHP was determined using a Reversed Phase HPLC assay specific for DEHP.The four tested administration-sets labeled as PVC-free, were all found to be suitable for Taxol^® application. The tested standard PVC-lined administration-set should not be used for Taxol^® application. Baxter Intermate^® LV 250 can be recommended as a disposable infusion device for ambulatory Taxol^® application. It can be connected with all the tested filter sets.     

The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets

The objective of this study was to identify and evaluate key polymer properties affecting direct compression and drug release from water-insoluble matrices. Commonly used polymers, such as Kollidon^® SR, Eudragit^® RS and ethyl cellulose, were characterized, formulated into tablets and compared with regard to their properties in dry and wet state. A similar site percolation threshold of 65% v/v was found for all polymers in dry state. Key parameters influencing polymer compactibility were the surface properties and the glass transition temperature (T_g), affecting polymer elasticity and particle size-dependent binding. The important properties observed in dry state also governed matrix characteristics and therefore drug release in wet state. A low T_g (Kollidon^® SR < Eudragit^® RS) decreased the percolation threshold, particle size effect and tortuosity, but increased permeability and sensitivity to heat/humidity treatment. Hence, lower permeability and higher stability are benefits of a high-T_g polymer (ethyl cellulose). However, release retardation was observed in the same order as matrix integrity (Eudragit^® RS < ethyl cellulose < Kollidon^® SR), as the high permeability was counteracted by PVP in case of Kollidon^® SR. Therefore, the T_g and composition of a polymer need to be considered in polymer design and formulation of controlled-release matrix systems.     

Effect of anti-inflammatories on Pluronic F127: micellar assembly, gelation and partitioning

We present results on the effect of two anti-inflammatory agents, naproxen and indomethacin, on the structure, assembly and gelation transitions of Pluronic F127 micelles. Small-angle neutron scattering experiments on micellar solutions indicate that the micelle aggregation number decreases significantly in the presence of drug solutes, causing the number density of micelles to increase. However, only slight changes were observed in the critical micelle concentration of F127 in the presence of these drugs. Both anti-inflammatory agents were found to shift the liquid-to-gel and gel-to-liquid transitions of the copolymer to lower temperatures. This may be the result of an increase in the micellar volume fraction, caused by the presence of the hydrophobic drugs. Using an ultraviolet spectroscopy technique, we have also measured the solubilities and micelle-water partition coefficients (Kmw) of naproxen and indomethacin in water and F127 solutions. The values of Kmw for naproxen and indomethacin are 355 +/- 64 and 474 +/- 33, respectively. They are larger than previously reported lipid-water partition coefficients, indicating that F127 micelles may be a better choice for drug loading than lipid vesicles. The slightly greater effects of indomethacin on the gelation boundary as compared with naproxen may be attributable to a higher value of Kmw.     

Effects of liquisolid formulations on dissolution of naproxen

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor^® EL (polyoxyl 35 castor oil), Synperonic^® PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel^® PH102 was used as a carrier material, Cab-o-sil^® M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor^® EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor^® EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised.     

助悬剂用量对糠酸氟替卡松鼻喷剂喷雾特性的影响

目的 研究混悬型鼻喷剂中助悬剂Avicel^®浓度对鼻喷剂喷雾模式、喷雾形态以及雾滴粒径的影响。方法 制备不同Avicel^®浓度的糠酸氟替卡松鼻用混悬液。通过SprayVIEW^®喷雾测试系统测试鼻喷剂的喷雾特性参数,使用Box-Behnken响应面法分析Avicel^®浓度对鼻喷剂体外喷雾特性的影响,同时考察Avicel^®浓度对喷雾雾滴粒径的分布影响以及在不同检测距离下雾滴的粒径变化。结果 增大Avicel^®浓度会显著减小喷雾面积以及喷雾角度和宽度（P<0.001）,同时增大D₅₀和整体粒径。增大驱动速度会显著增大喷雾面积、喷雾角度和宽度（P<0.05）,驱动加速度对喷雾特性的影响远小于Avicel^®浓度和驱动速度。随着检测距离的增加,雾滴粒径分布变得更加集中,雾滴粒径分布跨度变小。结论 本研究通过Box-Behnken响应面法发现Avicel^®的浓度与驱动速度对喷雾特性的影响存在拮抗作用,为鼻喷剂Avicel^®浓度的选择以及装置推荐驱动参数提供了参考。     

Inhibition of surface crystallisation of amorphous indomethacin particles in physical drug–polymer mixtures

Surface coverage may affect the crystallisation behaviour of amorphous materials. This study investigates crystallisation inhibition in powder mixtures of amorphous drug and pharmaceutical excipients. Pure amorphous indomethacin (IMC) powder and physical mixtures thereof with Eudragit^® E or Soluplus^® in 3:1, 1:1 and 1:3 (w/w) ratios were stored at 30 °C and 23 or 42% RH. Samples were analysed during storage by X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, and scanning electron microscopy (SEM). IMC Eudragit^® mixtures showed higher physical stability than pure IMC whereas IMC Soluplus^® mixtures did not.     

Solubilisation of Drugs in Micellar Systems Studied by Eluent Gel Permeation Chromatography

Purpose. The purpose of the study was to investigate the potential of a chromatographic method which is based on elution gel chromatography (EGPC) in the study of solubilisation of drugs in micellar solutions. Methods. The EGPC method differs from conventional GPC in the use of a solution of the associating surfactant as eluent (rather than solvent) and the injection of a small volume of solution of different concentration (or alternatively injection of solvent alone) to probe the association equilibrium in the eluent. The technique was applied to a study of the solubilisation of selected drugs in aqueous micellar solutions of a triblock copolymer (Synperonic-PE F127) composed of oxyethylene [E, OCH₂CH₂] and oxypropylene [P, OCH₂CH(CH₃)] units with nominal molecular formula E₉₈P₆₇E₉₈. Results. EGPC curves were obtained showing vacancy peaks at the elution volumes of the drugs, clearly demonstrating their solubilisation. In addition, the micelle-molecule equilibrium of the copolymer surfactant could be monitored at all times. Quantitative determination of the partition of solute between micelles and solvent phase was not possible due to the incomplete conversion of molecules to micelles in solutions of the selected copolymer. Conclusions. The EGPC technique provides evidence for the solubilisation of the drugs in aqueous solutions of Synperonic F127; a more thorough assessment of its potential for quantitative measurement of solubilisation requires the use of a surfactant which is wholly (or at least mainly) in the micellar state under the conditions of use.     

Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation,characterization and application in a vaginal drug delivery system

Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH₂) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH₂-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH₂ is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH₂ and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.     

Ion-Pairing Interactions between 99MTc-Based Myocardial Imaging Agents and Oleic Acid

Purpose. The purpose was to test the hypothesis that ion-paired facilitated transport is of importance in successful myocardial uptake of cationic imaging complexes. In vitro ion-pairing interactions between oleic acid and seven cationic technetium-99m complexes based on the ligands l,2-bis[bis(2-ethoxyethyl) phosphino ethane] (tetrofosmin), l,2-bis(dimethyl phosphino ethane) (DMPE) and l,2-bis(diethyl phosphino ethane) (DEPE) has been studied. The complexes studied were: [^99mTc O₂ (tetrofosmin)₂]⁺ (commercially available as myocardial perfusion imaging kit, Myoview^®), [^99mTc O₂ (DMPE)₂]⁺, [^99mTc O₂ (DEPE)₂]⁺, [^99mTc C1₂ (DMPE)₂]⁺, [^99mTc C1₂ (DEPE)₂]⁺, [^99mTc (DMPE)₃]⁺ and [^99mTc (DEPE)₃]⁺. Methods. Ion-pairing interactions were monitored using a rotating diffusion cell containing a solid supported liquid membrane and by formation of lipid monolayers. Results. Depletion of complex from the donor phase into an isopropyl myristate model membrane was generally in proportion to distribution coefficient and transfer to the receptor compartment was in all cases very small. However, by the inclusion of 5%w/v oleic acid, which is used in myocardial metabolism, partitioning was enhanced by amounts which varied depending on the tendency to form complex/oleate ion-pairs. Transfer to the receptor compartment was increased for most complexes when given sufficient time to diffuse through the membrane. The complex [^99mTc O₂ (tetrofosmin)₂]⁺ appeared to form particularly stable ion-pairs with oleic acid. Monolayer formation also indicated ion-pairing interactions. Conclusions. The results suggested that whether or not a complex is taken up by the myocyte may depend on its ability to hitch a ride by ion-pairing with the myocytes energy source—a molecule of long chain fatty acid.     

Determination of the Composition of Delavirdine Mesylate Polymorph and Pseudopolymorph Mixtures Using 13C CP/MAS NMR

Purpose. The application of solid-state nuclear magnetic resonance for the quantitation of relative amounts of delavirdine mesylate (DLV-M) polymorph and/or pseudopolymorph in their binary mixtures is presented. Methods. ¹³C CP (cross-polarization)/MAS (magic angle spinning) NMR techniques were employed for quantitation. Results. ¹³C CP/MAS NMR spectra of three DLV-M solid forms (VIII, XI, and XII) revealed distinct differences in chemical shifts and peak splitting characteristics. Resonances of isopropyl methyl carbons of DLV-M were diagnostic of each form; resonance intensities were utilized to determine the composition of two series of DLV-M solid form mixtures (VIII and XI; XII and XI) over a dynamic concentration range (1–50%). The empirical detection limit of form VIII, or XII, in a dominant form XI environment was about 2–3% (w/w). Quantitations were obtained using appropriate analytical procedures, which took into account the differences of T_CH and T_lpH between the two forms. Quantitative results obtained using either the peak area or peak height were examined, and, in general, were satisfactory. Conclusions. The methodology and analytical procedure developed in this study are generally applicable to quantitative analysis using ¹³C CP/MAS NMR for pharmaceutical solids, including bulk drug substances, and dosage forms. Reliable measurement of NMR relaxation times (T_1pH) and CP rate constants (T_CH) of individual forms is a critical component in this application.     

Properties of Free Films Prepared from Aqueous Polymers by a Spraying Technique

A spray method for the preparation of free films from aqueous polymeric dispersions was investigated. Free films were prepared from aqueous dispersions of methacrylic acid-ethyl methacrylate copolymer (Eudragit^® L 30D), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), and ethyl cellulose (EC) by a spray method and a cast method, and their mechanical properties and reproducibility were investigated. Uniform films were obtained from the dispersions of Eudragit^® L 30D, HPMCAS, and EC by the spray method, but films could not be formed by spraying the CAP dispersion. The tensile strength, elongation, and elastic modulus of the sprayed Eudragit^® L 30D films were similar to the properties of the cast films, and good reproducibility was obtained from both methods. Marked within-run variation in the mechanical properties was observed for the cast HPMCAS and CAP films, which could be due to a settling of the solid particles during the drying step. The variation in the mechanical properties of the sprayed HPMCAS films was lower and the tensile strength significantly higher than that of the cast films. There were also significant differences in tensile strength and elongation of EC films between products of the two methods. The results indicated that the spray method used to prepare the free films from aqueous polymeric dispersions provided uniform films with consistent and reproducible properties.